Hydroxyl groups are one of the key factors for the development of coal self-heating, although their detailed reaction pathways are still unclear. This study investigated the reaction pathways in coal self-heating by the method of quantum chemistry calculation. The Ar–CH2–CH(CH3)–OH was selected as a typical structure unit for the calculation. The results indicate that the hydrogen atoms in hydroxyl groups and R3–CH are the active sites. For the hydrogen atoms in hydroxyl groups, they are directly abstracted by oxygen. For hydrogen atoms in R3–CH, they are abstracted by oxygen at first and generate peroxy-hydroxyl free radicals, which abstract the hydrogen atoms in hydroxyl groups later. The reaction of R3–CH contains three elementary reactions, i.e., the hydrogen abstraction of R3–CH by oxygen, the conjugation reaction between the R3C■ and oxygen atom, and the hydrogen abstraction of –OH by hydroxyl free radicals. Then, the microstructure parameters, IRC pathways, and reaction dynamic parameters were respectively analyzed for the four reactions. For the hydrogen abstraction of –OH by oxygen, the enthalpy change and activation energy are 137.63 and 334.44 kJ/mol, respectively, which will occur at medium temperatures and the corresponding heat effect is great. For the reaction of R3–CH, the enthalpy change and the activation energy are −3.45 and 55.79 kJ/mol, respectively, which will occur at low temperatures while the corresponding heat influence is weak. They both affect heat accumulation and provide new active centers for enhancing the coal self-heating process. The results would be helpful for further understanding of the coal self-heating mechanism.